Nevin Manimala

Ann Hematol. 2022 Jul 2. doi: 10.1007/s00277-022-04908-6. Online ahead of print.

ABSTRACT

Peripherally inserted central venous catheters (PICCs) have a potential advantage in preventing central line-associated bloodstream infection (CLABSI) compared with the centrally inserted ones (CICCs). However, due to a limited number of studies with insufficient statistical evaluation, the superiority of PICCs is difficult to be generalized in adult hematology unit. We conducted a single-center retrospective study and compared the risk of CLABSI between 472 CICCs and 557 PICCs inserted in adult patients with hematological disorders through conventional multivariate models and a propensity score-adjusted analysis. The overall CLABSI incidence in CICCs and PICCs was 5.11 and 3.29 per 1000 catheter days (P = 0.024). The multivariate Cox regression analysis (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.31-0.75; P = 0.001) and Fine-Gray subdistribution analysis (HR: 0.59; 95% CI: 0.37-0.93; P = 0.023) demonstrated that PICC was independently associated with a reduced risk of CLABSI. Moreover, the stabilized inverse probability of treatment weighting analysis, which further reduced the selection bias between CICCs and PICCs, showed that PICCs significantly prevented CLABSI (HR: 0.58; 95% CI: 0.35-0.94; P = 0.029). Microbiologically, PICCs showed a significant decrease in gram-positive cocci (P = 0.001) and an increase in gram-positive bacilli (P = 0.002) because of a remarkable reduction in Staphylococci and increase in Corynebacterium species responsible for CLABSI. Our study confirmed that PICC was a superior alternative to CICC in preventing CLABSI in the adult hematology unit, while it posed a microbiological shift in local epidemiology.

PMID:35780253 | DOI:10.1007/s00277-022-04908-6

Contracept Reprod Med. 2022 Jul 3;7(1):12. doi: 10.1186/s40834-022-00180-1.

ABSTRACT

BACKGROUND: We conducted a single-centered randomized controlled single-blinded trial (i.e. trained interviewers; blinded to group allocation). The target population included adolescent girls in the Kumbo West Health District (KWHD) of Cameroon. This trial tested the efficacy of weekly educational one-way text messages to improve perception of adolescent girls on sexo-reproductive health.

METHODS: Allocation concealment (1:1) was determined by sequentially numbered sealed opaque envelopes. A total of 398 participants either received the mobile phone sexo-reproductive health text messages (199) or not (199). A blinded program secretary send out text messages and recorded delivery. Data was collected and managed at baseline and at 6 month intervals using an interviewer-administered questionnaire before and after intervention, then analysed using the independent T-test (mean differences) and ANOVA on SPSS version 21.

RESULTS: The mean knowledge, attitude and practice scores respectively increased significantly from 6.03, 4.01 and 3.45 at baseline to 7.99, 5.83 and 4.99 at the end of the study. After performing ANOVA for the overall correct knowledge, positive attitudes and good practices respectively for between and within the intervention groups, we obtained: (F = 15.12, P = 0.023), (F = 60.21, P = 0.001) and (F = 57., P = 0.013) which showed statistical significance thus indicating the overall improvement in adolescents girls perception as a result of the intervention and not by chance. Majority (65.3%) of the participants were satisfied with the Short Message Service (SMS).

CONCLUSION: This trial has contributed to the body of knowledge and evidence on the use of mobile phone technology using educative SMS to improve adolescent girl’s perception on sexo-reproductive health in Cameroon.

TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201805003259293 . Registered 28 March 2018.

PMID:35780241 | DOI:10.1186/s40834-022-00180-1

Eur Arch Paediatr Dent. 2022 Jul 2. doi: 10.1007/s40368-022-00720-y. Online ahead of print.

ABSTRACT

PURPOSE: Τo assess the outcome of direct pulp capping in asymptomatic carious primary molars using three pulp capping materials.

METHODS: In this prospective clinical trial, carious primary molars free of irreversible pulp inflammation signs and symptoms, with negative pain history and pulp exposure following caries removal were included. Teeth were divided into groups: A: Ca(OH)₂, B: Pure Portland cement^®, C: Biodentine™. Following anaesthesia, isolation, caries removal, pulp exposure, hemorrhage control, pulp capping, additional lining in groups A, B, teeth were restored with composite resin. Descriptive statistics, Chi-squared and Fisher’s exact tests, Kaplan-Meier survival curves, multivariable random effects Cox regression model were performed.

RESULTS: Sixty-six patients (25 girls, 41 boys) with mean age 7.2 (± 1.7) years participated. The mean follow-up time was 13 months. Seventy-nine primary molars were assigned to groups A (n = 27), B (29), C (n = 23). The overall failure was 16% and the distribution by group was: A: 5 teeth, B: 5 teeth, C: 3 teeth. No significant differences in failure rates between capping materials, tooth types, age bands and genders were identified.

CONCLUSIONS: Direct pulp capping in asymptomatic carious primary molars may be an acceptable option, when treating an exposed pulp with bioceramic materials as pulp capping agents.

PMID:35780237 | DOI:10.1007/s40368-022-00720-y

Med Microbiol Immunol. 2022 Jul 2. doi: 10.1007/s00430-022-00744-7. Online ahead of print.

ABSTRACT

In the fight against coronavirus infection, control of the immune response is of decisive importance, an important component of which is the seroprevalence of antibodies to SARS-CoV-2. Immunity to SARS-CoV-2 is formed either naturally or artificially through vaccination. The purpose of this study was to assess the seroprevalence of antibodies to SARS-CoV-2 in the population of Kyrgyzstan. A cross-sectional randomized study of seroprevalence was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the Association of Preventive Medicine (Kyrgyzstan) and the St. Petersburg Pasteur Institute (Russia) approved the study. Volunteers (9471) were recruited, representing 0.15% (95% CI 0.14-0.15) of the total population, randomized by age and region. Plasma antibodies (Abs) to the nucleocapsid antigen (Nag) were determined. In vaccinated individuals, Abs to the SARS-CoV-2 receptor-binding domain antigen (RBDag) were determined. Differences were considered statistically significant at p < 0.05. The SARS-CoV-2 Nag Ab seroprevalence was 48.7% (95% CI 47.7-49.7), with a maximum in the 60-69 age group [59.2% (95% CI 56.6-61.7)] and a minimum in group 1-17 years old [32.7% (95 CI: 29.4-36.1)]. The highest proportion of seropositive individuals was in the Naryn region [53.3% (95% CI 49.8-56.8)]. The lowest share was in Osh City [38.1% (95% CI 32.6-43.9)]. The maximum SARS-CoV-2 Nag seropositivity was found in the health-care sector [57.1% (95% CI 55.4-58.8)]; the minimum was seen among artists [38.6% (95% CI 26.0-52.4)]. Asymptomatic SARS-CoV-2 Nag seropositivity was 77.1% (95% CI 75.6-78.5). Vaccination with Sputnik V or Sinopharm produced comparable Ab seroprevalence. SARS-CoV-2 Nag seropositivity in the Kyrgyz population was 48.75% (95% CI 47.7-49.7), with the mass vaccination campaign undoubtedly benefitting the overall situation.

PMID:35780233 | DOI:10.1007/s00430-022-00744-7

Nat Commun. 2022 Jul 2;13(1):3832. doi: 10.1038/s41467-022-31653-1.

ABSTRACT

Plant alkaloids constitute an important class of bioactive chemicals with applications in medicine and agriculture. However, the knowledge gap of the diversity and biosynthesis of phytoalkaloids prevents systematic advances in biotechnology for engineered production of these high-value compounds. In particular, the identification of cytochrome P450s driving the structural diversity of phytoalkaloids has remained challenging. Here, we use a combination of reverse genetics with discovery metabolomics and multivariate statistical analysis followed by in planta transient assays to investigate alkaloid diversity and functionally characterize two candidate cytochrome P450s genes from Atropa belladonna without a priori knowledge of their functions or information regarding the identities of key pathway intermediates. This approach uncovered a largely unexplored root localized alkaloid sub-network that relies on pseudotropine as precursor. The two cytochrome P450s catalyze N-demethylation and ring-hydroxylation reactions within the early steps in the biosynthesis of diverse N-demethylated modified tropane alkaloids.

PMID:35780230 | DOI:10.1038/s41467-022-31653-1

Ann Surg Oncol. 2022 Jul 2. doi: 10.1245/s10434-022-12035-9. Online ahead of print.

ABSTRACT

BACKGROUND: Secondary lymphedema is a debilitating morbidity. This study investigated the outcomes of vascularized lymph node transfer (VLNT) in elderly patients with secondary upper extremity lymphedema.

METHODS: Between 2008 and 2018, elderly (≥65 years) patients with secondary upper extremity lymphedema who underwent VLNT were retrospectively reviewed. Cheng’s Lymphedema Grading, Taiwan Lymphoscintigraphy Staging, and indocyanine green lymphography were used to select the procedures. Outcome measurements included complications, circumferential difference, episodes of cellulitis, and the Lymphedema-Specific Quality of Life questionnaire (LYMQoL).

RESULTS: Eleven patients with a mean age of 70.2 ± 5.3 years (range 65-80 years) who underwent VLNT survived and no major complications were encountered. At a mean follow-up of 6.5 ± 3.6 years (range 2-13 years), the mean limb circumferential difference was significantly improved from 25.6 ± 11.5% to 8.3 ± 4.2% (p = 0.016), and the mean episode of cellulitis was statistically reduced from 2.4 ± 1.3 to 0.4 ± 0.9 times/year (p = 0.007). At a follow-up of 24 months, four domains of Function (from 30.6 ± 2.8 to 14.5 ± 2.5), Appearance (from 18.2 ± 1.9 to 8.5 ± 2.1), Symptoms (from 30.4 ± 5.9 to 10.9 ± 1.0) and Mood (from 29.2 ± 4.4 to 10.7 ± 1.0), as well as overall LYMQoL score (from 3.9 ± 1.1 to 7.4 ± 0.5), showed statistical improvement (all p < 0.05).

CONCLUSIONS: VLNT for secondary upper extremity lymphedema in elderly patients significantly decreased the limb circumferential difference and frequency of cellulitis and improved quality of life without using compression garments postoperatively.

PMID:35780215 | DOI:10.1245/s10434-022-12035-9

Nat Commun. 2022 Jul 2;13(1):3817. doi: 10.1038/s41467-022-31236-0.

ABSTRACT

Long diagnostic wait times hinder international efforts to address antibiotic resistance in M. tuberculosis. Pathogen whole genome sequencing, coupled with statistical and machine learning models, offers a promising solution. However, generalizability and clinical adoption have been limited by a lack of interpretability, especially in deep learning methods. Here, we present two deep convolutional neural networks that predict antibiotic resistance phenotypes of M. tuberculosis isolates: a multi-drug CNN (MD-CNN), that predicts resistance to 13 antibiotics based on 18 genomic loci, with AUCs 82.6-99.5% and higher sensitivity than state-of-the-art methods; and a set of 13 single-drug CNNs (SD-CNN) with AUCs 80.1-97.1% and higher specificity than the previous state-of-the-art. Using saliency methods to evaluate the contribution of input sequence features to the SD-CNN predictions, we identify 18 sites in the genome not previously associated with resistance. The CNN models permit functional variant discovery, biologically meaningful interpretation, and clinical applicability.

PMID:35780211 | DOI:10.1038/s41467-022-31236-0

Sci Rep. 2022 Jul 2;12(1):11219. doi: 10.1038/s41598-022-15549-0.

ABSTRACT

Systemic lupus erythematosus (SLE) is the prototype of an autoimmune disease. Belimumab, a monoclonal antibody targets BAFF, is the only biologic approved for SLE and active lupus nephritis. BAFF is a cytokine with a key-regulatory role in the B cell homeostasis, which acts by binding to three receptors: BAFF-R, TACI and BCMA. TACI and BCMA also bind APRIL. Many studies reported elevated soluble BAFF and APRIL levels in the sera of SLE patients, but other questions about the role of this system in the disease remain open. The study aimed to investigate the utility of the cytokine levels in serum and urine as biomarkers, the role of non-functional isoforms, and the association of gene variants with the disease. This case-control study includes a cohort (women, 18-60 years old) of 100 patients (48% with nephritis) and 100 healthy controls. We used ELISA assays to measure the cytokine concentrations in serum (sBAFF and sAPRIL) and urine (uBAFF and uAPRIL); TaqMan Gene Expression Assays to quantify the relative mRNA expression of ΔBAFF, βAPRIL, and εAPRIL, and next-generation sequencing to genotype the cytokine (TNFSF13 and TNFSF13B) and receptor (TNFRSF13B, TNFRSF17 and TNFRSF13C) genes. The statistical tests used were: Kruskal-Wallis (qualitative variables), the Spearman Rho coefficient (correlations), the Chi-square and SKAT (association of common and rare genetic variants, respectively). As expected, sBAFF and sAPRIL levels were higher in patients than in controls (p ≤ 0.001) but found differences between patient subgroups. sBAFF and sAPRIL significantly correlated only in patients with nephritis (r_s = 0.67, p ≤ 0.001) and βAPRIL levels were lower in patients with nephritis (p = 0.04), and ΔBAFF levels were lower in patients with dsDNA antibodies (p = 0.04). Rare variants of TNFSF13 and TNFRSF13B and TNFSF13 p.Gly67Arg and TNFRSF13B p.Val220Ala were associated with SLE. Our study supports differences among SLE patient subgroups with diverse clinical features in the BAFF/APRIL pathway. In addition, it suggests the involvement of genetic variants in the susceptibility to the disease.

PMID:35780200 | DOI:10.1038/s41598-022-15549-0

Sci Rep. 2022 Jul 2;12(1):11212. doi: 10.1038/s41598-022-15062-4.

ABSTRACT

Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients’ clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease’s features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with > 1 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had ≥ 2 autoantibody positivity, and 2.3% (n = 72) had ≥ 2 SSc-Abs positivity. Th e most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.

PMID:35780179 | DOI:10.1038/s41598-022-15062-4

Nat Commun. 2022 Jul 2;13(1):3816. doi: 10.1038/s41467-022-31572-1.

ABSTRACT

Although urban greening is universally recognized as an essential part of sustainable and climate-responsive cities, a growing literature on green gentrification argues that new green infrastructure, and greenspace in particular, can contribute to gentrification, thus creating social and racial inequalities in access to the benefits of greenspace and further environmental and climate injustice. In response to limited quantitative evidence documenting the temporal relationship between new greenspaces and gentrification across entire cities, let alone across various international contexts, we employ a spatially weighted Bayesian model to test the green gentrification hypothesis across 28 cities in 9 countries in North America and Europe. Here we show a strong positive and relevant relationship for at least one decade between greening in the 1990s-2000s and gentrification that occurred between 2000-2016 in 17 of the 28 cities. Our results also determine whether greening plays a “lead”, “integrated”, or “subsidiary” role in explaining gentrification.

PMID:35780176 | DOI:10.1038/s41467-022-31572-1